Toward understanding the symbiotic role of microbial communities in - PowerPoint PPT Presentation

Toward understanding the symbiotic role of microbial communities in human biology Ma ría Glo ria Do míng ue z-Be llo NYU Sc ho o l o f Me dic ine

“First picture of Earth from the surface of Mars” NASA’s Curiosity rover, Jan 31 st 2014

Biology-driven evolution Origin Multicelular life Origin Eukaryotes Homo sapiens of Earth 2.1 billion years ago of first life 0.2 million years ago 4.8 billion 3.8 billion years ago years ago BACTERIA

Body niches for the human microbiome Costello et al. 2009 Science

Epithelia covers animal bodies

Developmental exposures and selection pressures Maternal Environmental Vaginal skin- oral + strict milk seeding >6 months 0-6 months Newborn 1 month 2 months 4 months 7 months

Developmental exposures and selection pressures Vaginal seeding skin- oral + strict milk >6 months 0-6 months Newborn 1 month 2 months 4 months 7 months

Developmental exposures 1-MOM 2-MILK 3-BUILT ENVIRONMENT The New Yorker, Nov 4, 2015

The primate tree of life and hominid subsistence Gatherers Gatherers - Hunters (0.2) (Million years (2.5) ago) (4) p (6) (8) (15)

Bipedalism Features that made us human: Cooperativism Gatherers Gatherers - Hunters (0.2) (Million years (2.5) ago) (4) p (6) (8) (15)

Bipedalism and pelvis constraints Gatherer 4 2.5 0.2 M years of common ancestor

Cooperation and brain size D. Lieberman, 2013

Big head + Narrow pelvis ~15% births D. Lieberman, 2013

C-section and maternal mortality The Economist, August 2015

C-section rates variation in Europe, 2010

C-section rate changes in Sweden and the USA 1996 2009 2012 SWEDEN 17% (2008) USA USA 30% (2008)

Effect of delivery mode on the neonate’s primary microbiota?

Acquisition of maternal vaginal microbiota 1 2 3 4 Mother-baby pair PNAS 2010

Mode of birth and primary microbiota PNAS 2010

Mode of birth and primary microbiota Va g ina l C-se c tio n PNAS 2010

Mode of birth and primary microbiota Va g ina l C-se c tio n ? PNAS 2010

Bacterial source: the built environment? Hakdong Shin New York Univ. Humberto Cavallin Univ. Puerto Rico Shin et al 2015 PloS One

Human skin bacteria in Operating Room dust Distances between groups PC2 (6%) (***, p<0.001) HMP_Skin *** *** *** HMP_Oral OR samples vs HMP_Vaginal Operating room samples (n=30) HMP_Skin (n=2,199) HMP_Stool HMP_Oral (n=3,695) HMP_Vaginal (n=564) 0.6 0.8 1.0 HMP_Stool (n=437) PC1 (16%) Unweighted UniFrac Distance - Unweighted - 1,000 seqs/sample Shin et al 2015 PloS One - Closed-reference OTU picking

Human skin flakes in Operating Room dust Positive control OR swabs Negative control 10 um 10 um 10 um H/E staining 10 um 10 um 10 um Pan-cytokeratin Shin et al 2015 PloS One

Kassandra de Jesus Lavoy Restoring the microbiome of C-section newborns Vaginal source C-section Nora Henderson Sukhleen Bedi NYU

Vaginal seeding of babies born by C-section C-section C-section + vaginal gauze Dominguez-Bello et al 2016 Nature Medicine

Vaginal seeding of babies born by C-section

Inclusion criteria for patients in the clinical study • Scheduled C-section (maternal choice, previous C-section or malposition presentation) • Healthy mothers with healthy pregnancy • Negative for HIV, Group B Streptococcus (GBS), active primary herpes, gonorrhea, chlamydia and other STDs, bacterial vaginosis • Vaginal pH ≤ 4.5 at time of delivery

Beta diversity of vaginal gauze microbes in relation to maternal body sites Dominguez-Bello et al 2016 Nature Medicine

Bacterial sources in the first month of life Vaginal delivery Exposed C-section (n=7) (n=4) (n=7) Dominguez-Bello et al 2016 Nature Medicine

Bacterial sources in the first month of life Vaginal delivery Exposed C-section (n=7) (n=4) (n=7) Dominguez-Bello et al 2016 Nature Medicine

Proportion of bacterial taxa in the first month of life Days Dominguez-Bello et al 2016 Nature Medicine

Proportion of infant bacterial taxa in the first month of life Sp Sp Sp La La La La Ba S24-7 La S24-7 S24-7 Ba Ba Ba DELIVERY Sp Sp Sp La La La S24-7 S24-7 La S24-7 Ba La Ba Ba Ba Days Dominguez-Bello et al 2016 Nature Medicine

Restoration of some bacterial taxa at age 1 month Dominguez-Bello et al 2016 Nature Medicine

Does “seeding” of C-section babies protect ? from C-section associated diseases

Type 1 diabetes Diseases associated Algert, McElduff et al. 2009 Aumeunier, Grela et al. 2010 with C-section Bonifacio et al. 2012 Celiac disease Decker, Engelmann et al. 2010 Marild, Stephansson et al. 2012 Asthma Kero, Gissler et al. 2002 Kero et al. 2002 Thavagnanam et al. 2007 Roduit et al. 2009 Couzin-Frankel 2010 Ege et al. 2011 Azad et al. 2012 Obesity Huh, Rifas-Shiman, et al. 2012 Blustein et al. 2013 Mueller et al 2014

Growing incidence of immune disorders in developed countries Bach 1999

Infant microbiome diversity variation with age PD Whole Tree Observed Species p=0.012 p=0.015 70% 70% p=0.121 p=0.176 p=0.500 p=0.929 p=0.310 p=0.702 p=0.190 p=0.811 p=0.400 p=0.833 p=0.692 p=0.132 p=0.555 p=0.985 p=0.193 p=0.149 p=0.211 p=0.970 Infant age (mo) VD n=13 CS n=10 ECAM study Infants not exposed to antibiotics Blaser group

Pa ine e t a l 1998, E c o syste ms Gut Mic ro b io ta fo r He a lth Summit Ba rc e lo na , Ma rc h 14-15. Re silie nc e E xtinc tio ns E xtinc tio ns

Is the urbanite microbiome impacted?

Fecal microbiota diversity in three human populations Adults Babies <6-months Yatsunenko et al 2012, Nature

Most Isolated peoples Photo: Maria G Dominguez-Bello

Contemporary 1975 tribal cultures Uncontacted peoples Venezuela 2008 Brazil Paraguay

Yanomami village – first contact Photos: Oscar Noya 2008

Gut microbiome diversity across cultures Westernization Clemente et al. 2015 Science Advances

Gut microbiome diversity across cultures Westernization Clemente et al. 2015 Science Advances

HUMAN MICROBIOME PROJECT

Developmental exposures 1-MOM 2-MILK 3-BUILT ENVIRONMENT The New Yorker, Nov 4, 2015

Developmental exposures VS

Developmental exposures VS

MICROBES ACROSS CULTURES

Home bacterial composition differs by urbanization level Ruiz et al 2016 Science Advances

Bacterial communities of wall-floors converge with urbanization Ruiz et al 2016 Science Advances

Wall bacteria in house spaces Houses Ruiz et al 2016 Science Advances

Changes in developmental exposures Reduced maternal Transmission Reduced exposure to environmental microbes Reduced microbiota diversity Increased chronic immune diseases

Biology-driven evolution Origin Multicelular life Origin Eukaryotes Homo sapiens of Earth 2.1 billion years ago of first life 0.2 million years ago 4.8 billion 3.8 billion years ago years ago BACTERIA

Biology-driven evolution Urbanite Origin Multicelular life Origin Eukaryotes Homo sapiens of Earth 2.1 billion years ago of first life 0.2 million years ago 4.8 billion 3.8 billion years ago years ago BACTERIA Culture-driving evolution

Urbanite Biology-driven evolution 30,000 y Origin Multicelular life Origin Eukaryotes Homo sapiens of Earth 2.1 billion years ago of first life 0.2 million years ago 4.8 billion 3.8 billion years ago years ago BACTERIA Culture-driving evolution

Evolution turns the inevitable into a necessity Jacques Monod

Alfred P. Sloan Foundation Supporting team Emch Research Fund C&D Research Fund Oscar Noya Hakdong Shin Marina Hoashi Carlos Lopez Kassandra de Jesus Laboy Central Univ. of Venezuela NYU NYU Noraliz Garcia Ana Maldondado Albertorio Univ Puerto Rico Juan L Rivera Correa Jean Frances Ruiz Selena Rodriguez Univ Puerto Rico Henrique Pereira Univ. Fed Amazonas Atila Novoselac Univ. Texas-Austin Luciana Paulino Humberto Cavallin Univ Puerto Rico Martin Blaser Se Jin Song Jose CLemente Rob Knight NYU Univ. Colorado Mount Sinai S.M. UCSD Sloan project team, Peru-Brazil, USA